GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas

Area of Science:

• Oncology
• Genetics
• Ophthalmology

Background:

• GNAQ mutations are implicated in various vascular malformations and melanocytic neoplasms.
• Port wine stains and ocular melanocytic neoplasms share GNAQ mutations.

Purpose of the Study:

• To investigate the presence and specific types of GNAQ mutations in diffuse (Sturge-Weber syndrome-associated) and solitary choroidal hemangiomas.
• To compare GNAQ mutation patterns in different types of choroidal hemangiomas and related conditions.

Main Methods:

• Next-generation sequencing (NGS) was employed to analyze formalin-fixed, paraffin-embedded tumor specimens from 11 patients.
• Digital PCR was utilized for targeted detection of GNAQ Q209 mutations in one specimen.
• Specimens included port wine stains, diffuse choroidal hemangiomas, solitary choroidal hemangiomas, and choroidal nevi.

Main Results:

• Activating somatic GNAQ mutations (p.Arg183Cys) were detected in 100% of port wine stains and the single diffuse choroidal hemangioma.
• Somatic GNAQ mutations (p.Gln209Leu) were found in 100% of solitary choroidal hemangiomas.
• A different GNAQ mutation (p.Gln209Pro) was identified in the choroidal nevus specimen.

Conclusions:

• GNAQ mutations are a common feature of both diffuse and solitary choroidal hemangiomas.
• Diffuse choroidal hemangiomas harbor GNAQ mutations at the R183 codon, aligning with other Sturge-Weber syndrome-related vascular malformations.
• Solitary choroidal hemangiomas exhibit GNAQ mutations at the Q209 codon, similar to other intraocular melanocytic neoplasms.